Non-steroidal anti-inflammatory drugs (NSAID viz. indomethacin, flurbiprofen) decrease urinary calcium excretion in male Sprague-Dawley rats. Indomethacin decreases significantly the urinary calcium excretion in hypercalciuric patients. These observations encouraged the use of NSAID in the treatment of nephrolithiasis with encouraging initial results. However, NSAID (indomethacin and naproxen) retard both glycosaminoglycans (GAGs) synthesis and degradation thereby causing a significant reduction in the urinary excretion of GAGs, known to be potent inhibitors of calcium oxalate crystallization. Therefore, the effect of another NSAID, diclofenac-Na (50 mg t.i.d. for 4 weeks) was studied on 31 recurrent calcium oxalate nephrolithiasis patients who were not hypercalciuric or hyperuricosuric. The 24-h urinary excretion of creatinine, calcium and uric acid remained unchanged at 2 weeks and 4 weeks of therapy. However, after treatment of 2 weeks and 4 weeks, there was a significant decrease in the 24-h urinary excretion of GAGs (from 17.04 +/- 7.39 mumol to 11.54 +/- 7.02 and 12.7 +/- 6.2 mumol, respectively), and urinary concentration of GAGs (from 10.77 +/- 7.09 mumol/l to 6.03 +/- 5.00 mumol/l and 7.35 +/- 4.81 mumol/l, respectively). Thus diclofenac-Na (50 mg t.i.d.) did not reduce urinary excretion of calcium but significantly lowered the urinary excretion and concentration of GAGs in normocalciuric nephrolithiasis patients, an observation which cautions against the use of diclofenac-Na in prevention of nephrolithiasis in this group of patients.